The goal of this research is to develop novel, biologically functional nanostructures that dramatically enhance the reproducibility, sensitivity, and spatial density of chip based assays. These nanostructures will improve applications ranging from point-of-care diagnosis to genomic arrays used in basic research by enabling the development of next generation screening technologies that are faster, more sensitive, more reliable, and possibly more cost effective than those presently available in the life sciences market. To accomplish the stated goals, Nanolnk will develop a patterning methodology based on Dip Pen Nanolithography (tm)(DPN(tm)) technology to generate sub-micron sized features on solid surfaces. The DPN method, built upon the technique of Atomic Force Microscopy (AFM), allows one to deposit materials uniformly in a direct-write fashion on surfaces with nanoscale spatial precision. This strategy offers significant advantages over current microarray printing technologies that suffer from poor spot to spot reproducibility in terms of size, shape, and oligonucleotide density, as well as reproducibility across microarray slides. In Phase I, Nanolnk demonstrated the feasibility of an approach based on DPN technology by generating sub-micron scale DNA nanostructures on glass surfaces. The resulting nanostructures were analyzed using existing fluorescence probe technology to provide benchmarking standards for comparison to conventional microarray assays. Concurrent with ink development and patterning optimization, microfabricated parallel multipen arrays were developed as a means for faster, simultaneous writing of multiple DNA inks. In Phase II, Nanolnk will develop a nanoarray fabrication platform consisting of a nanoarrayer instrument, parallel multipen arrays with integrated microfluidic inking systems and appropriate pen and surface modification chemistry to allow patterning with a variety of biomolecules. The Phase II effort will build on our success in Phase I and yield a flexible, nanoarray fabrication "system" with both near term and long term commercial potential. A commercialization partner has been identified for Phase III. This research project will develop a system for fabricating biochip microarrays that will offer more sensitive and reliable tools for medical research groups helping them to better understand the role of genes and proteins in human health. Improved methods of diagnosing and treating disease will result. [unreadable] [unreadable] [unreadable]